Skeletal muscle imaging in neuromuscular disease

doi:10.1016/j.jocn.2016.01.041

Journal of Clinical Neuroscience

Volume 33, November 2016, Pages 1-10

https://doi.org/10.1016/j.jocn.2016.01.041 Get rights and content

Highlights

•
Muscle ultrasound (US) and MRI are complementary to clinical and electrodiagnostic evaluation of neuromuscular disease.
•
US has benefits of portability for clinic-based use, and dynamic imaging for assessing normal and abnormal muscle movements.
•
MRI has the benefit of distinguishing between water- and fat-based muscle pathologies.
•
Changes on muscle MRI and US may be quantified for objective disease monitoring and research applications.
•
Anatomical distribution of muscle abnormalities may provide clues for diagnosis of genetic and inflammatory muscle diseases.

Abstract

Skeletal muscle imaging is increasingly used as a complement to clinical and electrophysiological examination in neuromuscular disease. Ultrasound and MRI have developed as the modalities of choice, each with strengths and limitations. Characteristic changes of muscle denervation and myopathy are seen on imaging which may delineate the nature of the disease process or help guide muscle biopsy. Identifying patterns of muscle involvement in hereditary myopathies may inform genetic testing. This review discusses skeletal muscle imaging in neuromuscular disease focusing on practical applications of current and emerging ultrasound and MRI techniques.

Introduction

The evaluation of a patient with a suspected neuromuscular disease relies on a combination of clinical history, physical examination, and ancillary testing, often including electrodiagnostic evaluation. With advances in the quality and availability of radiologic technology, imaging of muscles has a growing role in the evaluation of patients with suspected neuromuscular disorders. Muscle imaging often detects abnormalities suspected based on the physical exam but can also identify unsuspected pathologies. Muscle imaging can be used to screen multiple muscles to identify the presence and pattern of pathology to either inform the differential diagnosis directly or to direct the electrodiagnostic evaluation or muscle biopsy.

Muscle imaging is most commonly performed using MRI or ultrasound. Both MRI and ultrasound are painless, radiation-free modalities to identify neuromuscular pathology. Ultrasound can be obtained by the examiner at the bedside in the clinic setting and dynamic features of muscle can be explored. MRI allows for better imaging of deep structures and by applying different sequences can distinguish water and fat based pathologies.

Both MRI and ultrasound are used more commonly than either X-ray or CT scanning. X-rays are suboptimal for detecting most neuromuscular pathologies but can detect skeletal abnormalities and intramuscular calcifications. CT scan of muscle can detect fatty degeneration and atrophy characteristic of some myopathies or chronic denervation. Both X-ray and CT scans expose the patient to radiation without much advantage over MRI or ultrasound in the diagnosis and evaluation of neuromuscular disease. This article will therefore focus on ultrasound and MRI imaging of skeletal muscle.

Section snippets

Muscle ultrasound

Ultrasound has well recognized advantages of being a painless imaging modality that can be quickly applied at the bedside. The current availability of portable systems that are capable of providing good-quality high-resolution images has brought about a major shift in the application of imaging in the neuromuscular clinic from clinician-requested to clinician-directed. Specifically, the same clinician responsible for the clinical and neurophysiological diagnosis increasingly performs the

Muscle MRI

Muscle MRI compensates for its lack of convenience by the structural detail provided and the availability of specialized sequences to more precisely delineate the nature of the pathologic process.

T1-weighted MRI sequences produce high-resolution anatomical images of the muscle. Fat is bright on T1-weighted MRI, and as such are ideal to demonstrate the fatty replacement of muscle characteristic of many myopathies (Fig. 3B). T1-weighted MRI sequences will not give an indication of inflammation or

Quantitative muscle imaging

Quantitative imaging assessments of muscle, provides improved reliability and sensitivity for neuromuscular disease and allows for measurement of the degree of muscle pathology. Muscle imaging as a surrogate measure of disease activity is appealing for studying patients who are too young or too weak to participate in assessments based on strength and function but must also be sensitive enough to detect the slow progression seen in many neuromuscular disorders over time. Quantification of muscle

Imaging of specific neuromuscular disorders

Many myopathies have characteristic and highly selective patterns of muscle involvement [58], [59], [60]. A combination of history, physical exam, histopathology and increasingly, genetic testing will be sufficient to determine the diagnosis. In some patients, identifying the pattern of muscle involvement may help with the diagnostic process, such as improving diagnostic confidence, refining genetic testing, or in selecting appropriate sites for biopsy. The clinical examination is sometimes

Conclusions

This review highlights the practical applications of skeletal muscle imaging in neuromuscular disease. Qualitative and quantitative ultrasound and MRI techniques have a defined role in the diagnosis of muscle injury, including identifying evidence of muscle denervation and myopathy, delineating patterns of muscle involvement in hereditary myopathies, and optimizing muscle selection for biopsy. Further, quantitative imaging techniques may provide objective measures to evaluate disease

Conflicts of Interest/Disclosures

The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.

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Muscle MRI and ultrasound provide complementary techniques for characterizing muscle changes and tracking disease progression in facioscapulohumeral muscular dystrophy (FSHD). In this cohort study, we provide longitudinal data that compares both imaging modalities head-to-head.
FSHD patients were assessed at baseline and after five years. Standardized muscle MRI and ultrasound images of five leg muscles were assessed bilaterally. Fat replacement was quantified using MRI fat-fraction (FF) and ultrasound Heckmatt and echogenicity z-scores (EZ-score). Muscle edema was evaluated using T₂-weighted turbo inversion recovery magnitude (TIRM) MRI.
Twenty FSHD patients were included. Muscles with normal baseline imaging showed increases in ultrasound EZ-scores (≥1; in 17%) more often than MRI FF increases (≥10%; in 7%) over time. Muscles with only baseline ultrasound abnormalities often showed considerable FF increases (in 22%), and TIRM positivity at follow-up (44%). Muscles with increased FF at baseline showed stable (80%) or increasing FF (20%) over time. EZ-scores of those muscles either increased (23%), decreased (33%) or remained stable (44%).
Muscle ultrasound may capture accelerated pathological muscle changes in FSHD in early disease, while muscle MRI appears better-suited to detecting and monitoring pathology in later stages.
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Establishing the role of muscle ultrasound as an imaging biomarker in facioscapulohumeral muscular dystrophy
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Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary muscle disease, that causes weakness and wasting of skeletal muscles. In this cross-sectional cohort-study on FSHD patients, we assessed muscle ultrasound findings and their relation to clinical outcome measures, evaluating the role of ultrasound as biomarker in FSHD. We included 115 genetically confirmed FSHD patients (52% males, age-range 22–80 years). They were subjected to a standardized muscle ultrasound protocol of seven truncal and upper- and lower extremity muscles bilaterally. Muscle images were scored using the Heckmatt scale. Muscle echogenicity was quantified using z-scores. Compound echogenicity and Heckmatt scores were calculated. Nearly all patients (94%) had one or multiple muscles with an increased echogenicity z-score. The trapezius muscle was most severely affected, followed by the rectus femoris muscle. Both compound ultrasound scores strongly with multiple clinical outcome measures (ρ 0.68–0.79, p < 0.001). While most muscles showed a high level of agreement between the echogenicity z-score and Heckmatt score (>95%), the tibialis anterior and gastrocnemius muscle showed lower levels of agreement (82 and 92%). In conclusion, our study confirms the use of muscle ultrasound as clinical severity biomarker and provides a solid base for future longitudinal studies to establish ultrasound as a monitoring biomarker in FSHD.
Muscle Ultrasound Changes Correlate With Functional Impairment in Spinal Muscular Atrophy
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We investigated ultrasound patterns of muscle involvement in different types of spinal muscular atrophy (SMA) and their correlation with functional status to determine the pattern of muscle compromise in patients with SMA and the potential role of ultrasound to evaluate disease progression.
We examined muscles (biceps brachii, rectus femoris, diaphragm, intercostals and thoracic multifidus) of 41 patients with SMA (types 1 to 4) and 46 healthy age- and sex-matched control individuals using B-mode ultrasound for gray-scale analysis (GSA), area (biceps brachii and rectus femoris) and diaphragm thickening ratio. Functional scales were applied to patients only. We analyzed ultrasound abnormalities in specific clinical subtypes and correlated findings with functional status.
Compared with controls, patients had reduced muscle area and increased mean GSA for all muscles (p < 0.001), with an established correlation between the increase in GSA and the severity of SMA for biceps brachii, rectus femoris and intercostals (p = 0.03, 0.01 and 0.004 respectively) when using the Hammersmith Functional Motor Scale Expanded. Diaphragm thickening ratio was normal in the majority of patients, and intercostal muscles had higher GSA than diaphragm in relation to the controls.
Ultrasound is useful for quantifying muscular changes in SMA and correlates with functional status. Diaphragm thickening ratio can be normal even with severe compromise of respiratory muscles in quantitative analysis, and intercostal muscles were more affected than diaphragm.
Muscle ultrasound in hereditary muscle disease
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In this context, the diagnosis of hereditary muscle diseases is increasingly reliant on muscle imaging. Both MRI and ultrasound can demonstrate muscle tissue abnormality, characteristic patterns of muscle involvement and track changes longitudinally [2]. The real time, non-invasive nature, relative low cost, and lack of ionizing radiation make ultrasound well suited for flexible point of care and dynamic muscle assessments [3].
In this review we summarise the key techniques of muscle ultrasound as they apply to hereditary muscle disease. We review the diagnostic utility of muscle ultrasound including its role in guiding electromyography and muscle biopsy sampling. We summarize the different patterns of sonographic muscle involvement in the major categories of genetic muscle disorders and discuss the limitations of the technique. We hope to encourage others to adopt ultrasound in their care for patients with hereditary muscle diseases.
The relationship between quantitative magnetic resonance imaging of the ankle plantar flexors, muscle function during walking and maximal strength in people with neuromuscular diseases
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This may, at least partly, explain why maximal isometric strength and dynamic muscle function during walking are not strongly related in patient populations. Pathophysiological muscle changes can be non-invasively assessed using conventional Magnetic Resonance Imaging (MRI) in combination with Diffusion tensor imaging (DTI) and quantitative T2 mapping (Budzik et al., 2014; Morrow et al., 2016; Simon et al., 2016). DTI measures the diffusivity of water within tissue.
Progression of plantar flexor weakness in neuromuscular diseases is usually monitored by muscle strength measurements, although they poorly relate to muscle function during walking. Pathophysiological changes such as intramuscular adipose tissue affect dynamic muscle function independent from isometric strength. Diffusion tensor imaging and T2 imaging are quantitative MRI measures reflecting muscular pathophysiological changes, and are therefore potential biomarkers to monitor plantar flexor functioning during walking in people with neuromuscular diseases.
In fourteen individuals with plantar flexor weakness diffusion tensor imaging and T2 scans of the plantar flexors were obtained, and the diffusion indices fractional anisotropy and mean diffusivity calculated. With a dynamometer, maximal isometric plantar flexor strength was measured. 3D gait analysis was used to assess maximal ankle moment and power during walking.
Fractional anisotropy, mean diffusivity and T2 relaxation time all moderately correlated with maximal plantar flexor strength (r > 0.512). Fractional anisotropy and mean diffusivity were not related with ankle moment or power (r < 0.288). T2 relaxation time was strongly related to ankle moment (r = −0.789) and ankle power (r = −0.798), and moderately related to maximal plantar flexor strength (r < 0.600).
In conclusion, T2 relaxation time, indicative of multiple pathophysiological changes, was strongly related to plantar flexor function during walking, while fractional anisotropy and mean diffusivity, indicative of fiber size, only related to maximal plantar flexor strength. This indicates that these measures may be suitable to monitor muscle function and gain insights into the pathophysiological changes underlying a poor plantar flexor functioning during gait in people with neuromuscular diseases.
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View all citing articles on Scopus

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ReviewSkeletal muscle imaging in neuromuscular disease

Highlights

Abstract

Introduction

Section snippets

Muscle ultrasound

Muscle MRI

Quantitative muscle imaging

Imaging of specific neuromuscular disorders

Conclusions

Conflicts of Interest/Disclosures

J Pediatr

Clin Neurophysiol

Clin Neurophysiol

Clin Radiol

Clin Neurophysiol

Clin Neurophysiol

Clin Neurophysiol

Clin Neurophysiol

Ultrasound Med Biol

Clin Neurophysiol

Ultrasound Med Biol

Neuromuscul Disord

Eur J Ultrasound

Man Ther

Neuromuscul Disord

Lancet Neurol

Neuromuscul Disord

Arch Phys Med Rehabil

Neuromuscul Disord

Neuromuscul Disord

Neuromuscul Disord

Neuromuscul Disord

Neuromuscul Disord

J Neurol Sci

Ultrasound in the diagnosis of peripheral neuropathy: structure meets function in the neuromuscular clinic

J Neurol Neurosurg Psychiatry

Rise and fall of skeletal muscle size over the entire life span

J Am Geriatr Soc

Quantitative ultrasonography of skeletal muscles in children: normal values

Muscle Nerve

Skeletal muscle ultrasonography in children with a dysfunction in the oxidative phosphorylation system

Neuropediatrics

Advances in the neurological and neurosurgical management of peripheral nerve trauma

J Neurol Neurosurg Psychiatry

Quantitative ultrasound of denervated hand muscles

Muscle Nerve

Two-dimensional ultrasound imaging of the diaphragm: quantitative values in normal subjects

Muscle Nerve

Variability in diaphragm motion during normal breathing, assessed with B-mode ultrasound

J Orthop Sports Phys Ther

Sensitivity and specificity of diagnostic ultrasound in the diagnosis of phrenic neuropathy

Neurology

Fasciculation potentials in healthy people

Muscle Nerve

Fasciculation anxiety syndrome in clinicians

J Neurol

The puzzling case of hyperexcitability in amyotrophic lateral sclerosis

J Clin Neurol

Ultrasonographic detection of fasciculations markedly increases diagnostic sensitivity of ALS

Neurology

Detection of fibrillations using muscle ultrasound: diagnostic accuracy and identification of pitfalls

Muscle Nerve

Measurement of muscle contraction with ultrasound imaging

Muscle Nerve

Ultrasonographic assessment of human skeletal muscle size

Eur J Appl Physiol

Minimal training is required to reliably perform quantitative ultrasound of muscle

Muscle Nerve

Muscle ultrasound in neuromuscular disorders

Muscle Nerve

Review
Skeletal muscle imaging in neuromuscular disease